Please also note that, at the end of NEHA's Position Paper on Endocrine Disrupters, we have published a short counterpoint on the topic. Our purpose is to provide you with as much information as possible on this important and controversial subject.

Recent reports have indicated that many xenobiotics (man-made chemicals) in the environment are capable of disrupting the endocrine system not only in a wide variety of animals, but also in human beings. Some of the reported effects in humans include decreased sperm counts and increased cases of testicular cancer and testicular abnormalities, premature puberty in females and increased cases of endometriosis, and an increase in reproductive cancers (1­3). Perhaps the most well-known example of an endocrine disrupter is DES (diethylstilbestrol), which was administered to pregnant women to prevent premature birth (4). In 1970, an increased incidence of vaginal clear-cell carcinoma was reported in the female offspring of women who had taken DES in the first trimester of pregnancy (5). Since that time, mounting evidence suggests that, in many instances, the presence of certain xenobiotics has had additional deleterious, endocrine-disrupting effects on both human and wildlife populations (6).

The purpose of this position paper is to review current information on the status of endocrine disrupters, with particular emphasis on the implications for environmental and public health. It is intended to be used as a basis from which environmental and public health practitioners and colleagues in related fields can initiate discussions with policy makers at all levels; local, state, national, and worldwide.

Endocrine disrupters, also sometimes called environmental estrogens or estrogenic xenobiotics, influence many developmental and physiological responses at multiple sites of activity (6). Many of the endocrine disrupters discovered to date (Table 1) have an anthropogenic, that is, man-made, source. A major source of these compounds has been found to be sewage, in which approximately 3,000 out of a possible 60,000 man-made organic pollutants have been found (7­10). In addition to human beings, a number of animal species have also been affected by endocrine disrupters (Table 2). Some of the effects reported include blocking of the effects of male hormones, resulting in the demasculinization of male offspring; antithyroid effects; alterations in the adrenal gland; decreased sperm count in male offspring; structural abnormalities in the external genitalia of female offspring and delayed puberty in the male; defeminization and masculinization of female fish and birds; decreased hatching success in fish, birds, and turtles; decreased fertility in birds, fish, shellfish, and mammals; and gross birth deformities in birds, fish, and turtles (11­18).

• Encourage additional research in the field of developmental biology of hormonally responsive organs. Too little is known concerning what levels of endocrine-disrupting hormones elicit pathological changes in human beings and animals.
• Encourage inclusion of screening assays for hormonal activity in the testing of products for regulatory purposes. Banning the use and production of many endocrine-disrupting chemicals has not prevented exposure to these substances.
• Make reproductive effects and teratogenicity the prime factors in evaluating health risks. In the past, only cancer was considered as an important endpoint in evaluating health risks from exposure to chemicals in the environment.
• Increase public awareness, as well as the awareness of the scientific and medical communities, of the presence of endocrine disrupters. Often, the effects of these substances are not readily evident at birth and are not manifested until puberty or adulthood; in human beings, these

Upon adoption, the National Environmental Health Association (NEHA) should disseminate this paper as widely as possible by release to the membership, publication in the Journal of Environmental Health, provision of copies of this paper to affiliates to share with their members, and provision of copies of this paper to similar professional associations for their review. Affiliates and members should be encouraged to provide comments to legislators based on the information contained herein, or to provide a copy of this document as augmentation to their own comments.

The committee foresees the only fiscal impact on NEHA with the adoption of this paper to be the cost of making and mailing copies. The fiscal impact of the problem will be felt mainly by those individuals who suffer from the adverse effects of exposure to endocrine disrupters.

(Original paper prepared by Ginger L. Gist, Ph.D., D.A.A.S., Senior Environmental Health Scientist, Agency for Toxic Substances and Disease Registry.)

Table 1 Examples of Known and Potential Endocrine Disrupters

Substance	Reference	Substance	Reference
Diethylstilbestrol	5	DDT	20
PCBs	21	Estradiol-17b	22
Coumestrol	22	Equol	22
Zearalenone	22	3,9-Dihydroxybenz[a]anthracene	22
Kepone	22	DDE	23
Methoxychlor	20	Mirex	20
TCDD	24	Tributyltin	25, 26
Tamoxifen	27	Cadmium	28
Zearealonone	29	Benzo[a]pyrene	30
Lead	30	Arochlor 1254	30
Methyl mercury	31	PAHs	32
Polychlorinated dibenzo-p-dioxins	33	Polychlorinated dibenzofurans	33
Cyproterone acetate	29	Dibromochloropropane	29
Fenarimol	29	Nitrofen	29
Hexachlorophene	29	PBBs	29
Carbaryl	34	Aldrin	34
Chlordane	34	2,4-D	34
2,4,5-T	34	Zineb	34
Maneb	34

Table 2 Examples of Species That Have Been Affected by Endocrine Disrupters

Scientific Name	Common Name	Reference(s)
Nassarius obsoletus	Mud snail	35, 36
Larus occidentalis	Western gull	37-39
Sterna caspia	Caspian tern	40
Larus argentatus	Herring gulls	41
Nucella lapillus	Dog whelk	42-44
Gambusia affinis holbrookii	Mosquito fish	45-48
Catostomis commersoni	White sucker fish	49
Perca fluviatilis	Perch	50
Ardea herodias	Great blue heron	51
Oncorhynchus spp.	Pacific ocean salmon	52
Urospinax cinerea	American oyster drill	53
Homo sapiens	Human being	54-59
Asteria rubens	Sea stars	28
Parophrys vetulus	English sole	60
Gadus morhua	Atlantic cod	61
Pseudopleuronectus americanus	Winter flounder	26
Micropogonias undulatus	Atlantic croaker	30
Halichoerus grypus	Grey seal	31
Phoca groenlandica	Harp seal	63
Nereis virens	Polychaetes	32
Mytilis edulis L.	Mussel	64
Pleuronectus platessa	Plaice	65
Strongylocentrotus intermedius	Sea urchin	66, 67
Nucella spp.	Shoreline whelks	68-70
Phoca vitulina	Common seal	71
Phoca hispida	Baltic ringed seal	72

1. Sharpe, R.M., and N.E. Skakkebaek (1993), "Are Oestrogens Involved in Falling Sperm Counts and Disorders of the Male Reproductive Tract?" Lancet, 341:1392-1395.

2. Birnbaum, L.S. (1994), "Endocrine Effects of Prenatal Exposure to PCBs, Dioxins, and Other Xenobiotics: Implications for Policy and Research," Environmental Health Perspectives, 102:676-679.

3. Henderson, B.E., L. Bernstein, and R. Ross (1988), "Estrogens as a Cause of Human Cancer: The Richard and Linda Rosenthal Foundation Award Lecture," Cancer Research, 48:246-253.

4. Bern, H.A., "The Fragile Fetus," Chemically Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection, T. Colborn and C. Clement, eds., Princeton, N.J.: Princeton Scientific Publishing Co., pp. 9-15.

5. Herbst, A.L., and H.A. Bern, eds. (1981), Developmental Effects of Diethylstilbestrol (Des) in Pregnancy, New York: Thieme-Stratton.

6. Jobling, S., M.G. Parker, T. Reynolds, J.P. Sumpter, and R. White (1995), "A Variety of Environmentally Persistent Chemicals, Including Some Phthalate Plasticizers, Are Weakly Estrogenic," Environmental Health Perspectives, 103:582-587.

7. Purdom, C.E., V.J. Bye, N.C. Eno, P.A. Hardiman, J.P. Sumpter, and C.R. Tyler (1994), "Estrogenic Effects of Effluents from Sewage Treatment Works," Chemical Ecology, 8:275-285.

8. Donaldson, W.T. (1977), "Trace Organics in Water," Environmental Science Technology, 11:348-351.

9. Bedding, N.D., J.N. Lester, A.E. McIntyre, and R. Perry (1982), "Organic Contaminants in the Aquatic Environment 1: Sources and Occurrence," Science of the Total Environment, 25:143-167.

10. Kraybill, H.F. (1981), "Carcinogenesis of Synthetic Organic Chemicals in Drinking Water," Journal of the American Water Association, 73:370-372.

11. Gray, L.E. Jr., W. Kelce, and J.S. Otsby, "Antiandrogenic Effects of the Fungicide Vinclozolin on Sex Differentiation of the Rat," Toxicology and Applied Pharmacology.

12. O'Neil, W.M., and W.D. Marshall (1984), "Goitrogenic Effects of Ethylenethiourea on Rat Thyroid," Pesticides and Biochemical Physiology, 21:92-101.

13. Rehnberg, G.L., K.C. Booth, R.L. Cooper, J.M. Goldman, L.E. Gray, J.F. Hein, and W.K. McElroy (1988), "Effect of Linuron on The Brain-Pituitary-Testicular Reproductive Axis in the Rat," Toxicologist, 8:121.

14. Colby, H.D. (1988), "Adrenal Gland Toxicity: Chemically Induced Dysfunction," Journal of the American College of Toxicology, 7:45-69.

15. Peterson, R.E., G.L. Kimmel, and H.M. Theobald (1993), "Developmental and Reproductive Toxicity of Dioxins and Related Compounds: Cross-Species Comparisons," Critical Review of Toxicology, 23:283-335.

16. Gray, L.E. Jr., L.S. Birnbaum, W. Kelce, E. Monosson, and J.S. Ostby, "Perinatal TCDD Reduces Ejaculated and Epididymal Sperm Counts in Rats and Hamsters, But Does Not Affect Testosterone or Androgen Receptor Levels," Toxicology and Applied Pharmacology.

17. Gray, L.E. Jr., L.S. Birnbaum, J.J. Diliberto, W. Kelce, R. Marshall, and J.S. Otsby (1993), "Perinatal TCDD Exposure Alters Sex Differentiation in Both Female and Male LE Hooded Rats," Chemosphere, 14:337-340.

18. Colborn, T., and C. Clement, eds. (1992), Consensus Statement. Chemical ly Induced Alterations in Sexual and Functional Development: The Wildlife/Human Connection. Princeton, N.J.: Princeton Scientific Publishing Co., pp. 1-8.

19. Arnold, S.F., B.M. Collins, L.J. Guillette, D.M. Klotz, , and J.A. McLachlan, and P.M. Vonier (1996), "Synergistic Activation of Estrogen Receptor with Combinations of Environmental Chemicals," Science, 272:1489-1492.

Sidebar

In response to one of the biggest health scares of the 1990's, last year federal legislators passed amendments to the Safe Drinking Water Act and the Food Quality Protection Act.

The scare: Increased reports worldwide of altered endocrine function, such as lowered sperm counts and reproductive abnormalities caused by chemicals, termed "endocrine disrupters."

One study that initiated the greatest concern was from Tulane University in 1996 that suggested a 1,600-fold increase in risk of endocrine disruption when relatively small amounts of chemicals were combined. But, as has become true with other alarming reports, this scare may not be real after all.

In the July 25, 1997 issue of Science magazine, Dr. John A. McLachlan, one of the authors of the Tulane study, formally withdrew his original paper, stating "any conclusions drawn from this paper must be suspended until such time, if ever, the data can be substantiated."

In fact, other scientists around the globe have not been able to duplicate the Tulane study. Dr. Stephen Safe, professor of toxicology at Texas A & M University commented: "It is clear that the best science now points to the conclusion that the endocrine effects of environmental chemicals are less harmful than had been suggested."

The scientific investigation continues. The EPA's Endocrine Disrupter Screening and Testing Advisory Committee will still develop and implement a screening program for EPA to submit to Congress by August 1999, and the National Academy of Sciences study is scheduled to be released at the end of [1997]. According to Assistant EPA Administrator, Lynn Goldman, "The retraction does not eliminate the scientific basis for regulatory concern over endocrine-disrupting chemicals. Scientific and regulatory realities are not that simple." It appears that the endocrine disrupters scare may have just been the latest example of placing too much emphasis on one study.

(Source: Food Insight, September/October 1997)

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